The objectives of the proposed project are to understand how the developing mammalian fetus responds to chronic stresses such as those imposed by the presence of cardiovascular lesions. We wish, specifically, to analyze the effects of increased impedance to left ventricular outflow and the effects of decreased left ventricular inflow on the patterns of distribution of blood flow in the fetus, and on the growth and development of the myocardium and the circulation of the fetus. We have devised methods in pilot studies, for narrowing the ascending aorta and for narrowing the foramen ovale in fetal lambs. We plan to monitor the heart rates, the intracardiac and arterial blood pressures and blood gas tensions and the electrocardiograms for several weeks after the creation of one or the other of these cardiac lesions in these fetuses. Total cardiac output, the stroke volumes of each ventricle and the blood flow to each fetal organ will be measured at intervals by injections of radionuclide labeled microspheres (15 u diameter). The weights, wall thicknesses, volume capacities and statis compliances of each cardiac ventricle will be measured. The presence of myocardial hyperplasia and hypoplasia will be evaluated by the use of mitotic indices, by steriometric techniques and by autoradiography.